A Study to Assess the Safety, Tolerability, and Efficacy of ION-827359 in Participants With Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD) With Chronic Bronchitis (CB)
- Conditions
- Chronic BronchitisChronic Obstructive Pulmonary Disease
- Interventions
- Drug: Placebo
- Registration Number
- NCT04441788
- Lead Sponsor
- Ionis Pharmaceuticals, Inc.
- Brief Summary
The purpose of this study was to evaluate the effect of ION-827359 on forced expiratory volume in 1 second (FEV1) in participants with mild to moderate COPD with CB.
- Detailed Description
This was a multi-center, double-blind, placebo-controlled, randomized, Phase 2a study of ION-827359 in up to 180 participants. The participants were randomized to receive oral inhalation of either ION-827359 or placebo for up to 13 weeks. At the end of 13 weeks, participants entered a 10-week post-treatment evaluation period.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ION-827359 37.5 milligrams (mg) ION-827359 Single-dose of ION-827359 37.5 mg was administered by oral inhalation via nebulizer, once every week for up to 13 weeks. Placebo Placebo Single-dose of placebo was administered by oral inhalation via nebulizer, once every week for up to 13 weeks. ION-827359 75 mg ION-827359 Single-dose of ION-827359 75 mg was administered by oral inhalation via nebulizer, once every week for up to 13 weeks.
- Primary Outcome Measures
Name Time Method Change From Baseline to the Primary Time Point in Forced Expiratory Volume in 1 Second (FEV1) Compared to Placebo From Baseline up to average of Weeks 13 and 14 FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Baseline was defined as the last non-missing measurement prior to the first study drug administration. The primary time point was defined as the average of weeks 13 and 14. FAS=Full analysis set.
- Secondary Outcome Measures
Name Time Method Change From Baseline in the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Respiratory Symptoms (E-RS) Daily Symptom Diary Total Score to the Primary Time Point From Baseline up to average of weeks 13 and 14 The E-RS scale is a participant-reported outcome (PRO) designed to measure the symptoms of participants with chronic obstructive pulmonary disease (COPD). The E-RS utilizes 11 respiratory symptom items from the existing and validated 14-item EXACT, which measures symptoms of exacerbation. The E-RS total score quantifies respiratory symptom severity, and 3 domains assess breathlessness (comprised of 5 items, score range \[0-17\]), cough and sputum (comprised of 3 items, score range \[0-11\]), and chest symptoms (comprised of 3 items, score range \[0-12\]). The E-RS was collected on the daily e-diary. The total score was derived by summing the 11-item scores and ranged between 0 to 40 with higher values indicating severe respiratory symptoms. The primary time point was defined as the average of weeks 13 and 14.
Change From Baseline in the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) to the Week 14 Time Point From Baseline to Week 14 The CAT is an eight-item questionnaire that was completed by the participant and is designed to quantify the impact of COPD symptoms on the health status of participants. Each item is rated on a 6-point scale ranging from 0 (no impairment) to 5 (maximum impairment). The total CAT score is calculated by summing the scores of all items and ranges from 0 to 40. Higher scores indicate a severe condition (more severe impact of COPD on a participant's life).
Change From Baseline in St. George's Respiratory Questionnaire - COPD Specific (SGRQ-C) Total Score to the Week 14 Time Point From Baseline to Week 14 The SGRQ is a participant completed, a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in participants with obstructive airway disease. The shorter 40-item version (SGRQ-C) which does not specify a Recall Period and has been validated specifically for COPD participants was used in this study. It consists of 40 items each weighted from 0 to a possible maximum of 100. Items 1-7 produced the symptoms score, 9-12 the activity score, and items 8, 10, 11, 13 and 14 the impacts score. Each component sub-score was calculated as a percentage of the summed weights of each item out of the sum of the maximum possible weight for that component (range 0-100). The total score was calculated by summing the weights to all positive responses in each component, where a positive item indicated the presence of symptoms, expressed as a percentage (range 0-100). Higher scores indicated a worse outcome (more limitations)
Change From Baseline in Post-Bronchodilator FEV1 From Baseline to end of treatment (EOT) [Up to Week 14] Post-bronchodilator FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation after administration of bronchodilator. Baseline was defined as the last non-missing measurement prior to the first study drug administration.
Cmax: Maximum Observed Plasma Concentration for ION-827359 Days 1 and 85 Tmax: Time to Reach the Maximum Plasma Concentration for ION-827359 Days 1 and 85 AUC[0-24h]: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours for ION-827359 Days 1 and 85 Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) Based on Severity Up to Week 24 An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of medicinal (investigational) product, whether or not the AE is considered related to the medicinal (investigational) product. A TEAE is defined as any AE starting or getting worse on or after the first dose of the study drug. The severity of a TEAE was assessed by the investigator and classified into one of the following: mild, moderate, and severe.
Percentage of Participants With Clinically Significant Change in Laboratory Values Up to Week 24 Laboratory parameters for serum chemistry, hematology, urinalysis, coagulation, complement, and lipids were assessed.
Percentage of Participants With Clinically Significant Change in Vital Sign Parameters Up to Week 24 Vital signs included assessment of heart rate, blood pressure, respiratory rate, and temperature.
Percentage of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings Up to Week 24 ECG parameters of ventricular rate, PR interval, QRS duration, QT, or QTc were assessed.
Trial Locations
- Locations (15)
MECS Research GmbH
🇩🇪Berlin, Germany
Pneumologisches Studienzentrum Markgrafenstrasse
🇩🇪Berlin, Germany
Hamburger Institut far Therapieforschung GmbH
🇩🇪Hamburg, Germany
Queen Anne Street Medical Centre, Heart Lung Center
🇬🇧London, United Kingdom
PNEUMOLOGIE VARNSDORF s.r.o.
🇨🇿Varnsdorf, Czechia
KLB Gesundheitsforschung Lubeck GmbH
🇩🇪Lübeck, Germany
Plicni Ambulance Rokycany, s.r.o.
🇨🇿Rokycany, Czechia
ZMS-Zentrum fur medizinische Studien GmbH
🇩🇪Warendorf, Germany
Selye Janos Korhaz, Rendelointezet
ðŸ‡ðŸ‡ºKomarom, Hungary
Csongrad Megyei Mellkasi Betegsegek Szakkorhaza
ðŸ‡ðŸ‡ºDeszk, Hungary
Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH
🇩🇪Grosshansdorf, Germany
Plicni ambulance Kralupy
🇨🇿Kralupy Nad Vltavou, Czechia
CEFISPIRO s.r.o.
🇨🇿Lovosice, Czechia
MediTrial s.r.o.
🇨🇿Jindrichuv Hradec, Czechia
IKF Pneumologie Mainz Helix Medical Excellence Center Mainz
🇩🇪Mainz, Germany